CD8 positive T-lymphocytes play an important role in host immunity to viruses. Anti-viral TCD8+ recognize MHC class I molecules bound to peptides derived from a cytosolic pool of viral proteins. Concerning the delivery of antigenic peptides to MHC class I molecules, our studies have addressed two separate questions. First, since secreted viral proteins are co-translationally translocated into the endoplasmic reticulum (ER) and the ER has limited proteolytic machinery, the aim of this study is to determine how peptides are derived from secreted proteins. Second, there are two sources of antigenic peptides, native proteins and everything else. We have termed all the non-native sources, DRiPs, or defective ribosomal products. DRiPs consist of prematurely terminated polypeptides and misfolded polypeptides produced from translation products of bona fide mRNAs in the proper reading frame. The second aim of this project is to examine the nature of the substrate from which antigenic peptides are derived and the their contribution to antigen presentation. - Viral Immunity, vaccinia virus, influenza virus, cancer, T lymphocytes, immunodominance, antigen presentation/processing